Compliance meter for clinical evaluation of drugs

ABSTRACT

A device for signalling the ingestion of medicaments in tablet form packed in blister packs in which the various tablet compartments on one side are delimited by a metal foil sheet which is common to the pack as a whole. A sheet (12) of insulating material has provided therein holes (20) which are so arranged as to correspond to the positions of the tablets in the pack. Electrodes (10, 11) having an electrically conductive surface are disposed circumferentially around each hole on one side of the sheet. A first number (10) of these electrodes is mutually connected to a first signal conductor, and a second number of these electrodes is mutually connected to a second signal conductor. The foil (2) is arranged such that when a tablet is removed through a hole in the blister pack located in the device, an electric contact is made between an electrode of the first number of electrodes (10) and an electrode of the second number of electrodes (11) and therewith an electric connection is established between the first and the second signal conductors. The first conductors from all of the first number of electrodes (10) are mutually connected to a common first signal conductor (100), and the second signal conductors (110, 111, 112) are each connected to a respective input of a sensing circuit (FIG. 6).

When evaluating the usefulness of drugs, it is necessary to carry outlengthy and costly trials to establish their effectiveness and also toestablish any side-effects that they might have. In fact, it is notpossible to register new drugs and medicaments with governmentauthorities unless usefulness and a reasonable absence of side-effectscan be shown.

A particular difficulty encountered in trials of this nature derivesfrom the so-called placebo effect, which enables a patient to be helped,both subjectively and even objectively, with the aid of "sugar pills",provided that the patient believes that he has been administered with aneffective drug. It is doubtful that drugs can be effectively testedagainst the effect of placeboes, unless the doctor concerned is alsounaware of which tablets contain the placebo and which contain theactive drug, since otherwise the doctor may inadvertently divulge to thepatient, in some way or another, the fact that a particular tablet isnothing more than a placebo. The practice of double blind trials istherefore widespread and necessary.

An idea of the difficulties encountered when testing drugs is given bythe clinical observation that a patient administered with a placebo mayalso complain of side-effects resulting therefrom. In the case of onereported study in which patients were administered with placeboes, noless than a quarter of the patients concerned discontinued taking theplacebo, because of the side-effects felt to be caused thereby (Capel etal, J. Rheumatol. 6 (1979) 584-593).

The standard procedure in clinical drug trials is to supply the patientsconcerned with blister cards or charts containing the drug in tabletform, together with a prescription as to how many tablets should betaken and at what times. The patient is also instructed to make notesrelevant to the treatment. This is particularly important in the case ofshort-lived drugs, such as pain relieving drugs. One problem with suchpractices is that the patient may forget to make notes at the timesprescribed and attempt to rectify this omission at a later date, forinstance immediately prior to seeing his doctor. Cases are also knownwhere a patient who has forgotten to take his tablets, removes a fewfrom the blister chart and throws them away, thus pretending to havetaken the tablets and therewith avoiding the doctor's displeasure.

Consequently, it is an object of this invention to provide a compliancemeter with which many of the pitfalls experienced in drug trials can beavoided. By compliance is meant here the strict obedience of the patientin following the doctor's instruction as to the times when the drugs(tablets) are to be taken and in what quantities, or, in a relativesense, how the tablets were taken and when, in those cases, forinstance, when the patient was told to take a tablet when and if theneed was felt.

Known to the art are devices which signal to a patient when a tabletshould be taken and which stop signalling when the tablet is removedfrom the pack, these devices functioning in the manner of an alarmclock.

Some devices of this kind are constructed to receive a blister pack andmeans are provided for detecting when a blister pad is broken and atablet is freed therefrom, whereupon the "alarm clock" is switched offand is not restarted until the next time a tablet is to be taken.Examples of such devices are to be found in DE-A-33 35 301 and EP-A-0191 168.

Although such devices have been found practical from the aspect ofpatient treatment, thereby overcoming the forgetfullness of old or verysick patients, they are not particularly useful for the purpose of thepresent invention.

One particularly important advantage afforded by the present inventionis that it is thereby made possible to register the time at which atablet is taken from the blister pack and also the tablet which wastaken at that time. This is of particular value when the tabletsconcerned are a mixture of different tablets and, for instance, compriseplacebo tablets. For example, when testing the effect of pain relievingtablets which the patient or subject is allowed to take at will, it isextremely valuable to know the length of time which passes before afurther tablet is taken and also how this length of time varies with thetype of tablet taken. In accordance with the inventive concept, thesetimes are stored in a memory so as to enable them to be analyzed,therewith providing results which could hardly be otherwise obtained atreasonable cost.

In accordance with the invention, the device comprises a blister cardholder, means for pressing a tablet from the card, and an electricsensor located at each tablet position. Devices of this kind are knownto the art, e.g. from the aforesaid patent publications.

According to one preferred embodiment of the invention, the aluminumfoil which is normally present in such blister packs is used to make aconnection between electric contacts located in the pack holder.

According to one important feature of the invention, all of the tabletlocations can be sensed and a removed tablet identified. Preferably, aconductor or lead is drawn from each tablet location to a selectornetwork, such as to allow the tablets or tablet locations to be sensedindividually. This is of particular advantage when the aluminum foilpresent is used as a means of making electric contact, since once madethe contact can be maintained indefinitely. When using individualholder-mounted electric contact devices or switches which are arrangedso as to be activated only when a tablet is pushed from the pack, it maybe possible instead to use a multiplexed sensing system and therewith tolimit the number of input leads to one set of column leads and one setof row leads, as will be understood by those skilled in this art.

According to one advantageous embodiment, the inventive device isprovided with a lid provided with holes which correspond to the tabletpositions, which lid may either be collapsible or, together with thecontact-carrying card, form a pocket which will enable a blister pack tobe inserted from one side.

The device may also be provided with a code reading facility which iseffective in reading a code on the package. This code may have the formof a bar code, or a margin notch or recess code capable of being sensedby microswitches, which in other respects may be coordinated with thoseelectrical contact elements or switches which are closed automaticallyas the blister pack is opened.

According to one beneficial application, the inventive device is coupledto a computer equipped with a text screen and a keyboard or button bankthrough which a patient is able to answer questions concerning hiscondition, e.g. the level of pain felt, the computer being able to storeboth the drug intake of the patient and the result achieved, whichgreatly enhances the level of reliability, since the test is no longerreliant on the memory of the patient or his ability to make notes,especially when the patient is weakened by sickness. The use of such anauxiliary arrangement supplemented to a greater or lesser degree, incases of regular treatment, can also be effective in so reducing theextent of personal care as to enable patients who might otherwise needto be hospitalized to be cared for in their homes.

The invention will be understood more readily from the followingdescription of an exemplifying, non-limiting embodiment thereof.

FIG. 1 illustrates the principle of the known blister pack.

FIG. 2 illustrates the manner of removal of tablets from a blister packaccording to FIG. 1.

FIG. 3 shows part of a blister pack mounted in a device according to theinvention.

FIG. 4 shows part of a circuit card.

FIG. 5 illustrates a perforated circuit card provided with sensingelectrodes.

FIG. 6 illustrates an electronic circuit for sensing a device accordingto the invention.

FIG. 7 illustrates an inventive device with a blister pack mountedtherein.

A tablet 4 packed in a blister pack is shown in FIG. 1. The blister packhas a first plastic layer 1, which is normally transparent, and whichhas pressed therein recesses or alveoli 3 in which tablets 4 are placed.The alveoli are covered with aluminum foil 2 which is secured with anadhesive. When the foil is depressed by the finger in the direction ofthe arrow 5, the layer is deformed and the tablet 4 will be pushedthrough the aluminum foil 2, which deforms, bulges outwardly andsubsequently ruptures. FIG. 3 illustrates a type of blister pack inwhich the said layers are placed between two pieces of perforatedcardboard 6 and 7, which is particularly suitable in respect of thepresent invention. According to the invention, when in use the blisterpack lies on a sheet 12 of insulating material provided with holes whichlie opposite the locations of respective tablets. Electrodes 10 and 11are located at the edges of the holes. When the blister pack is brokenopen, as illustrated in FIG. 2, the aluminum foil will make electriccontact with the electrodes 10 and 11. In those cases when the blisterpack lacks a cardboard sheet, it will be necessary to include acardboard insert, in order to ensure that a space is obtained betweenthe foil 2 and the electrodes 10 and 11.

FIG. 5 illustrates a plate for a blister pack containing 28 tablet sitesor locations, there being 20 holes at each tablet location. Thepositioning of the electrodes and the requisite circuitry will be seenbest from FIG. 4. A multiple of electrodes, here 14, are arranged aroundthe holes 20 and are connected such that all alternate electrodes, theelectrodes 10, are mutually connected to a common first signalconductor, which will normally be grounded, via a grid net arranged onthe same side of the plate, which will normally be a circuit card. Theremaining electrodes, referenced 11, are mutually connected at eachtablet site or location to a conductor on the rear side, via metallizedholes, and form a multiple of second signal conductors, such as 110, 111and 112 in FIG. 4, the number of second signal conductors being equal tothe number of tablet locations.

Thus, when a tablet is removed from the pack, an electrical contact isestablished between the first signal conductor 100 and one of the secondsignal conductors, e.g. the conductor referenced 110 in FIG. 4 when thetablet is removed from the tablet location 50 shown in the top leftquadrant of FIG. 4.

FIG. 6 illustrates schematically the manner in which these "switches"are used, one for each tablet. For the sake of simplicity inillustration, only one such "switch" 50 has been shown, although it willbe understood that the number provided may equal the number of tabletlocations.

The circuitry illustrated in FIG. 6 incorporates five integratedcircuits 60-63 and 70 of the kind designated HC 151 (Motorola).

These integrated circuits each have eight signal inputs, three addressinputs and one output. Logic circuits ensure that for each possibledigital address, i.e. eight addresses, the state of one of the signalinputs is sensed (high or low), and the output will then show acorrespondingly high or low value. It will be seen from the Figure thatthe "switch" 50, which corresponds to a tablet location, will normallyfunction as an open switch, prior to taking a tablet from the pack. Inthis state of the switch, the other signal conductor of the switch isnot connected to ground, but has a high level due to being connected topositive voltage +V, via a resistance 51. The other signal conductor isconnected to one of the unmarked signal inputs on the circuit 60.

Each of all other signal conductors from the remaining tablet locations(not shown) is connected to a respective signal input on one of thecircuits 60, 61, 62 or 63. The device illustrated in FIG. 6 is thus ableto accommodate other signal conductors, to a total of 32.

A computer 75 is provided for reading all "switches", such as 50. Inoperation, digital signals are transmitted on six parallel outputs a-f.The three least significant bits d, e and f, are connected to the threeaddress inputs on the circuits 60, 61, 62 and 63. Each of the outputs A,B, C, D of these circuits 60, 61, 62 and 63 is connected to a respectivesignal input on the circuit 70, which is of the same type as the others.Thus, a signal input on each of the circuits 60-63 is indicated throughthe three least significant bits d, e, and f, and if, for instance, theillustrated "switch" 50 is closed (tablet removed), the output signal Afrom this switch will be high when indicated by the bits d, e and f.When the bits a, b and c, which are connected to the circuit 70, thenindicate the input A, a high signal will pass to the computer.

The computer is programmed to address the bit sites or locations insequence, for instance every tenth of a second. If a tablet signals thatthe "switch" is closed, the computer leaves the search loop and repeatsthe indication towards the signalled tablet location, e.g. seven times,in order to make absolutely certain that the tablet has been removed andthe switch closed, whereafter the identity of the tablet removed and thetime of its removal are stored in the memory of the computer.

The program may suitably be such that once a tablet has been removed,the computer will no longer include this particular location in itsperiodic search.

In accordance with a preferred embodiment, the inventive device alsoincludes four microswitches 80-83, which are activated by the edge ofthe pack upon its insertion. For instance, said edge may have providedtherein an opening which when located opposite one of the microswitches,causes the switch to be open, whereas the switch is closed in theabsence of such an opening. In this way, 14 mutually differentconfigurations can be recognized ("all open" will signal the absence ofthe pack, whereas "all closed" will signal that an uncoded and wrongtablet pack has been inserted)

The sensing arrangement illustrated in FIG. 6 is only an example of aconceivable circuit for sensing or detecting the removal of a tabletfrom the pack, and it will be understood that many other circuitembodiments are conceivable. This also applies to the codingpossibilities, which can be effected in other ways, e.g. through barcodes (e.g. type EAN) capable of being read when the package isinserted.

FIG. 7 illustrates a device 90 constructed in accordance with theinvention, and shows a blister pack 91 being inserted into the devicethrough an open flap 92. The tablet alveoli are available through holes93, the released tablets falling through holes (not shown) located inthe undersurface of the device. The device incorporates a light signalin the form of a signalling lamp 95 and an acoustic signal in the formof a buzzer 94, which will remind a patient that a tablet should betaken, i.e. ingested. Although not shown, the device may be providedwith means which enables it to be connected to a data collectingcomputer, either permanently or temporarily during a visit from thedoctor concerned.

FIG. 7 also shows a coding example. The blister pack of this embodimenthas formed therein two recesses 96, which as the pack is inserted intothe device adjust the mutual positions of two contact arms ofmicroswitches. When, e.g., a further two microswitches are present,their reading value will be the opposite and therewith enable theblister pack to be identified.

We claim:
 1. A device for signalling the ingestion of medicaments intablet form packed in blister packs in which the various tabletcompartments on one side are delimited by means of a metal foil sheetwhich is common to the pack as a whole, the device including a sheet(12) of insulating material having provided therein holes (20) which areso arranged as to correspond to the positions of the tablets in thepack; electrodes (10, 11) having an electrically conductive surface,said electrodes being disposed circumferentially around each hole on oneside of the sheet; a first number (10) of these electrodes beingmutually connected to a first signal conductor, a second number of saidelectrodes being mutually connected to a second signal conductor; thefoil (2) being arranged such that when a tablet is removed through ahole in the blister pack located in the device, an electric contact ismade between an electrode of the said first number of electrodes (10)and an electrode of the second number of electrodes (11) and therewithan electric connection is established between the first and the secondsignal conductors, the first conductors from all of said first number ofelectrodes (10) of the holes (20) being mutually connected to a commonfirst signal conductor (100), and the second signal conductors (110,111, 112) from the various holes (20) being each connected to arespective input of a sensing circuit (FIG. 6).
 2. A device according toclaim 1, wherein the insulating sheet is a circuit card which hasconductors drawn on both sides thereof and in which the first number ofelectrodes (10) are connected to the common first signal conductor, atleast essentially through conductors drawn on one side of the circuitcard, whereas the second number of electrodes (11) are connected to theinputs of the sensing circuit at least partly through conductors drawnon the other side of the circuit card.
 3. A device according to claim 1,wherein the sensing circuit includes for each second signal conductor aresistor (50), one end of which is connected to voltage source (+V), andan input of a sensing circuit (60-63); and a multiplex device forsensing the states of the various amplifiers, and wherein, with eachdetected change of state in respective circuits, corresponding to ashort circuit between a first (10) and a second (11) signal conductor, asignal (71) is sent to a detecting computer (75).
 4. A device accordingto claim 1, further comprising a code reading arrangement (80-83) forreading a code provided on the blister pack.
 5. A device according toclaim 4, wherein the code reader comprises a plurality of contactdevices which are adapted to be influenced by the presence and absenceof recesses (96) in an edge margin of the blister pack.